We hypothesize that there may be a variety of methods to enhance in vivo replication of HIV-1 in Macaca nemestrina by bypassing the natural anti-viral defenses in the peripheral blood of the juvenile or adult macaque. In one experiment, two macaques were inoculated with HIV-1 directly into the bone marrow. Once this infection was confirmed, an in vivo passage of bone marrow from the infected macaques into two nave macaques was done. Viral infection and seroconversion was confirmed in all four macaques; one macaque is still sero-reactive to a number of proteins on Western blot more the 19 months after inoculation. In another experiment, neonatal M. nemestrina were inoculated with HIV-1 both intravenously and intrarectally, the hypothesis being that the immature immune system of the neonate would be more likely to permit HIV-1 replication. After infection was confirmed in both infants, blood and lymph nodes were harvested, cells were isolated, and a virus stock was prepared for an in vivo passage into two additional neonatal M. nemestrina. This inoculation was again both intravenous and intrarectal, and the peak virus load was significantly higher than in the first pair of macaques. This procedure will be repeated again; lymph nodes and blood have been collected from the second pair of macaques and a virus stock is being prepared for second in vivo passage into neonatal M. nemestrina.